Heart rate: an important confounder of pulse wave velocity assessment

Arterial stiffness is a strong determinant of cardiovascular risk. Pulse wave velocity (PWV) is an index of arterial stiffness, and its prognostic value has been repeatedly emphasized. The purpose of the present study was to assess the effect of heart rate (HR) on PWV. Twenty-two subjects with a mean age of 77.8+/-8.4 (SD) years and permanent cardiac pacing were studied. In each subject, PWV was measured at 5 different pacing frequencies in the same session (60, 70, 80, 90, 100 bpm), the order of the various frequencies being randomly determined. Furthermore, to test the reproducibility, a repeat measurement of PWV was obtained in one randomly selected frequency. Blood pressure (BP) was measured by conventional means at each pacing frequency. PWV appeared fairly reproducible because no significant difference was disclosed between the 2 measurements obtained at the same HR level (P=0.5) and both measurements were strongly correlated (r=0.87, P<0.001). No significant BP variation was observed during pacing. There was a highly significant effect of HR on PWV estimated by a one-way, within-subjects analysis of variance (P=0.01). This study demonstrates that HR is an important factor in the intraindividual variation of PWV in elderly subjects. This raises methodological concern about the measurement of this parameter. Standardizing PWV for HR level seems mandatory if one wants to interpret PWV changes in clinical trials or in the follow-up of patients.     

Acute effect of DDD versus VVI pacing on arterial distensibility

Pulse wave velocity (PWV) is a new technique and frequently used today to determine the elastic distensibility of great arteries. Increased arterial stiffness and PWV have been proposed as possible mechanisms in the initiation and/or progression and/or complications of atherosclerosis and cardiovascular disease. We evaluated the acute effect of two frequently used pacing modes (DDD vs. VVI) on arterial distensibility using PWV. METHODS: Seventeen patients (age, 56 +/- 14 years) implanted with DDD pacemakers were included in the study. All patients were pacemaker dependent and continuously paced at the programmed rate. PWV was measured first in DDD mode, and then the mode was switched to VVI, and PWV was measured again at the same programmed heart rate as in the DDD mode. RESULTs: Although systolic blood pressure significantly decreased from 129 +/- 18 to 119 +/- 16 mm Hg (p = 0.001) after switching the mode from DDD to VVI, diastolic blood pressure (81 +/- 12 vs. 80 +/- 13 mm Hg; p = 0.38) did not change. In addition, PWV significantly increased from 11 +/- 2.46 m/s in DDD mode to 11.29 +/- 2.43 m/s (p = 0.01) after having been programmed to VVI mode. CONCLUSIONS: Our results suggest that VVI pacing increases PWV, and therefore decreases arterial distensibility, and thus may contribute to the development and progression of atherosclerosis.     

Evaluation of carotid-femoral pulse wave velocity: influence of timing algorithm and heart rate

Carotid-femoral pulse wave velocity (PWV), a measure of arterial stiffness, is determined from the time taken for the arterial pulse to propagate from the carotid to the femoral artery. Propagation time is measured variously from the foot of the waveform or point of maximum upslope. We investigated whether these methods give comparable values of PWV at rest, during beta-adrenergic stimulation, and pacing-induced tachycardia. In subjects at rest (n=43), values obtained using the foot-to-foot method (SphygmoCor system) were 1.7+/-0.75 m/s (mean+/-SD) greater than those obtained using the maximum slope (Complior system) at a mean value of 12 m/s. Isoprotenerol (0.5 to 1.5 microg/min; n=10), and pacing (in subjects with permanent pacemakers; n=11) increased heart rate but had differential effects on systolic blood pressure and pulse pressure. The increase in heart rate produced by isoprotenerol (18+/-3 bpm) and pacing (40 bpm) was associated with an increase in PWV measured using both systems (increases of 0.7+/-0.2 m/s and 0.9+/-0.2 m/s for SphygmoCor and Complior, respectively, during isoprotenerol and increases of 2.1+/-0.5 m/s and 1.1+/-0.2 m/s for SphygmoCor and Complior, respectively, during pacing, each P<0.001). Reanalysis of waveforms recorded from the Complior system using the foot-to-foot method produced similar values of PWV to those obtained with the SphygmoCor, confirming that the difference between these systems was attributable to the timing algorithm rather than other aspects of signal acquisition. Carotid-femoral PWV is critically dependent on the method used to determine propagation time, but this does not account for variation of PWV with heart rate.     

Heart rate regularisation in patients with permanent atrial fibrillation implanted with a VVI(R) pacemaker.

Irregularity of ventricular cycles is a cause of haemodynamic impairment and symptoms in patients with atrial fibrillation (AF). AIM OF THE STUDY: Aim of the study was to determine the optimal pacing rate to stabilise ventricular cycle length at rest in patients with chronic AF, bradycardiac symptoms and VVI pacing. METHODS: The compensatory pause (CP) in AF, as defined by Langendorf, was used as a reference value in pacing the heart. The spontaneous mean heart rate (MHR) was assessed with the PM OFF. The CP was then calculated with the pacing rate programmed at 40 bpm. Four pacing rates were tested: rate of the CP (RCP), RCP + 5 bpm, RCP - 5 bpm and RCP - 10 bpm. RESULTS: RCP provided a good estimate of the MHR (r = 0.92). Pacing percentage (P%) was 24 +/- 15% at the pacing rate of RCP - 10 bpm, 39 +/- 19% at RCP - 5 bpm, 63 +/- 17% at RCP, and 79 +/- 19% at RCP + 5 bpm (p < 0.001). The corresponding HR modestly increased from 65 +/- 13 bpm to 66 +/- 13 bpm (p = NS), 68 +/- 13 bpm (p < 0.001) and 71 +/- 13 bpm (p < 0.001), respectively. CONCLUSION: The RCP estimates, during pacing, what the spontaneous MHR would be. Ventricular stimulation at the RCP causes a high P%, stabilising cardiac cycles with a modest increase in HR.     

Heart rate dependence of aortic pulse wave velocity at different arterial pressures in rats

Arterial stiffness, as measured by aortic pulse wave velocity (PWV), is an independent marker of cardiovascular disease and events in both healthy and diseased populations. Although some cardiovascular risk factors, such as age and blood pressure, show a strong association with PWV, the association between heart rate (HR) and PWV is not firmly established. Furthermore, this association has not been investigated at different arterial blood pressures. To study effects of HR on aortic PWV at different mean arterial pressures (MAPs), adult (12 weeks; n=7), male, anesthetized Sprague-Dawley rats were randomly paced at HRs of between 300 and 450 bpm, at 50-bpm steps. At each pacing step, aortic PWV was measured across a physiological MAP range of 60 to 150 mmHg by infusing sodium nitroprusside and phenylephrine. When compared at the same MAP, increases in HR resulted in significant increases in PWV at all of the MAPs >80 mmHg (ANOVA, P<0.05), with the greatest significant change of 6.03±0.93% observed in the range 110 to 130 mmHg. The positive significant association between HR and PWV remained when PWV was adjusted for MAP (ANOVA, P<0.001). These results indicate that HR dependency of PWV is different at higher pressures than at lower pressures and that HR may be a confounding factor that should be taken into consideration when performing analysis based on PWV measurements.     

Carotid plaques, but not common carotid intima-media thickness, are independently associated with aortic stiffness.

OBJECTIVE: It has been suggested that non-invasive aortic stiffness measurements can be used as an indicator of atherosclerosis. The relationships of arterial stiffness with arterial wall hypertrophy and atherosclerosis however, have rarely been investigated in large-scale studies. The present study reports the associations of carotid arterial structure assessed by B-mode ultrasound with carotid-femoral pulse-wave velocity in hypertensive and non-hypertensive subjects. DESIGN AND METHODS: Free health examinations were performed on 564 subjects (age 58.2 +/- 10.8 years, 31.9% of women, 53.2% of all were hypertensive). Carotid-femoral pulse-wave velocity (PWV) was used to assess aortic stiffness. Carotid ultrasound examination included measurements (at sites free of plaques) of intima-media thickness (IMT) at the common carotid arteries (CCA), CCA-lumen diameter, and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: Subjects with carotid plaques had significantly higher mean sex-adjusted values of PWV than those without carotid plaques (12.7 +/- 0.2 versus 11.1 +/- 0.1 m/s, P < 0.001). Multivariate analyses showed that this association was independent of sex, age, height, body mass index, mean blood pressure, pulse pressure, diabetes, hypercholesterolaemia and smoking habits (P < 0.009). PWV was positively associated with CCA-IMT and CCA-lumen diameter in sex-adjusted analysis (partial correlation coefficients (r ) were respectively 0.39 and 0.42, P < 0.001 for each). However, the association of PWV with CCA-IMT, but not that with CCA-lumen diameter, disappeared after further adjustment for age and blood pressure measurements (mean blood pressure and/or pulse pressure). CONCLUSION: This study shows that there is a differential association of PWV with CCA-IMT and carotid plaques. The nature of the independent positive association between atherosclerosis and arterial stiffness should be thoroughly investigated.     

Haemodynamics of induced atrial fibrillation: a comparative assessment with sinus rhythm, atrial and ventricular pacing

The haemodynamics and myocardial lactate consumption during induced atrial fibrillation (AF) were studied in 10 patients with paroxysmal AF. Their mean age (+/- SD) was 61 +/- 5 years and none had clinical evidence of ischaemic or rheumatic heart disease. Compared with sinus rhythm, the onset of AF was associated with a reduction in systolic blood pressure (152 +/- 13 mmHg) in AF vs 169 +/- 23 mmHg in sinus rhythm, P less than 0.01). There was no consistent change in cardiac output at the onset of AF compared with sinus rhythm, but the cardiac output was lower compared with regular atrial pacing at rates similar to those of induced AF (3.85 +/- 0.76 vs 4.38 +/- 0.89 l min-1, P less than 0.02). Compared with sinus rhythm or rate-matched atrial pacing, AF was associated with an elevated pulmonary arterial pressure (24.2 +/- 5.6 mmHg in AF vs 17.9 +/- 14.4 mmHg in sinus rhythm, P less than 0.01) and pulmonary arterial wedge pressure (18.6 +/- 5.6 vs 9.7 +/- 3.9 mmHg, P less than 0.01). The haemodynamic changes during AF were similar to those seen during regular ventricular pacing at an equivalent rate, although the latter was associated with a lower systolic blood pressure (152 +/- 13 mmHg in AF vs 136 +/- 25 mmHg in ventricular pacing, P less than 0.05) and higher right atrial pressure (8.2 +/- 4.4 vs 11.5 +/- 7.5 mmHg respectively, P less than 0.05), presumably due to the deleterious effects of cannon 'a' waves.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of Heart Rate and Isoproterenol on Pulmonary Vein Flow Velocity Following Radiofrequency Ablation: A Doppler Color Flow Imaging Study

INTRODUCTION: Application of radiofrequency energy at pulmonary vein (PV) ostium during focal atrial fibrillation (AF) ablation procedures increases flow velocity due to PV narrowing. Factors unrelated to ablation that effect PV flow velocity have not been described. AIMS OF THE STUDY: The purpose of this study was to evaluate, using intracardiac echocardiography (ICE) imaging, the effect of isoproterenol (ISO) and heart rate (HR) on PV flow velocity Pre- and Post-ablation. METHODS AND RESULTS: In 31 patients with AF undergoing LA-PV ostial ablation involving at least one PV ostium, an ICE catheter was placed in the RA to image and detect PV flow. PV ostial peak velocity was assessed in sinus rhythm Pre-, Post-ablation, during and after ISO (up to 20 microg/min). To separate HR versus ISO effect, PV velocity was measured during atrial pacing (after HR returned to baseline) at pacing rate matching HR with ISO. PV ostial velocity was assessed with ISO and pacing in 30 non-ablated and 33 ablated PVs. Ostial velocities of non-ablated PVs during ISO infusion (117 +/- 42 cm/s) were greater ( p < 0.03) than those during atrial pacing (78 +/- 26 cm/s) at matched HR (116 +/- 20, range 92-150 bpm). Ostial PV flow velocities of ablated PVs increased from 59 +/- 17 (30-95) cm/s Pre- to 95 +/- 25 (58-136) cm/s Post-ablation. During ISO infusion PV flow velocities in ablated PVs (118 +/- 34 cm/s) were also greater ( p < 0.03) than those during atrial pacing (96 +/- 37 cm/s) at matched HR (116 +/- 14, range 92-130 bpm). Atrial pacing alone produced no significant difference in PV flow velocities measured Pre- or Postablation. CONCLUSION: ISO appears to increase ostial flow velocity of ablated and non-ablated PVs independent of HR effect. These effects are important to recognize when PV velocity is used as an index for interpreting the impact of PV ostial lesions on functionally significant PV narrowing.     

Enhanced external counterpulsation does not alter arterial stiffness in patients with angina

BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive treatment for angina that acutely augments diastolic pressure and reduces cardiac afterload. However, the mechanism of the sustained clinical benefit seen with this therapy is not known. HYPOTHESIS: The study aimed to determine whether EECP leads to an improvement in arterial stiffness. METHODS: In all, 22 men and 1 woman with angina (age 63.6 +/- 6.7 years, mean +/- SD) were studied prior to and after 35 h of EECP therapy over 7 weeks. We measured carotid-radial (C-R) pulse wave velocity (PWV), and aortic augmentation index (AI) was derived from radial and carotid artery waveforms using applanation tonometry. Seventeen patients underwent treadmill exercise testing before and after the 7 weeks of EECP. RESULTS: After EECP therapy, despite a significant improvement in treadmill exercise time and a reduction in systolic and diastolic blood pressures, there was no significant change in any arterial stiffness parameters: Mean C-R PWV was 8.4 +/- 0.8 m/s at baseline and 8.0 +/- 1.2 m/s after 7 weeks of EECP, mean change: -0.4, 95% confidence interval (CI): -1.0, + 0.2, p = 0.17. Mean radial-derived AI was 25.7 +/- 10.4% before and 24.6 +/- 10.8% after, mean change: +1.1%, 95% CI: -2.3, +4.5, p = 0.53. Median AI-carotid was 31.5% before and 28.7% after; median change: -0.5, interquartile range: -9.5, +3.5, p = 0.32. Nineteen patients returned for 6-month recordings; neither blood pressure nor arterial stiffness readings were significantly different from baseline. CONCLUSION: Enhanced external counterpulsation therapy does not significantly alter arterial stiffness. Other than an initial reduction in blood pressure, the sustained clinical benefit seen with this therapy is unlikely to be effected through alterations in arterial wall mechanical properties.     

Ethnic differences in arterial stiffness and wave reflections after cigarette smoking

BACKGROUND: Smoking increases plasma nicotine. Nicotine releases catecholamines and alters arterial distensibility. The nicotine intake per cigarette is greater and serum cotinine levels, the proximate metabolite of nicotine, are higher in Blacks than in Whites. We tested the hypothesis that cigarette smoking increases the pulse wave velocity (PWV), a marker of arterial stiffness, and the augmentation index (AI), a measure of wave reflection, more in Blacks than in Whites. METHODS: We matched Black (n = 30) and White (n = 30) smokers for age, gender, body mass index and height. We determined carotid-femoral PWV (PWVCF) and carotid-radial PWV (PWVCR) (Complior), the AI derived from the aortic pressure waveform (applanation tonometry, Sphygmocor), blood pressure, heart rate (HR) and cotinine levels before and after cigarette smoking. We also performed measurements in 16 participants after sham smoking. RESULTS: Smoking increased the AI, PWVCF and PWVCR in the whole population (all P < 0.05, n = 60). Increases in the AI and PWV were positively related to serum cotinine levels (all P < 0.05). Smoking increased serum cotinine (P = 0.01) and mean blood pressure (P = 0.03) more, but raised the HR to a lesser extent, in Blacks [+8 +/- 4 versus +13 +/- 6 beats/min in Whites (mean +/- SD), P = 0.01]. Blacks disclosed larger increases in AI adjusted for HR (Blacks, +7.2 +/- 8 versus Whites, +4.4 +/- 8%; P = 0.03), PWVCF (Blacks, +1.1 +/- 0.2 versus Whites, +0.6 +/- 0.3 m/s; P < 0.01) and PWVCR (Blacks, +1.4 +/- 0.1 versus Whites, +0.7 +/- 0.4 m/s; P < 0.01) normalized for the mean blood pressure. No changes were observed with sham smoking. CONCLUSIONS: Smoking acutely increases the PWV and AI in Blacks more than in Whites. Differences in nicotine metabolism and beta-adrenergic sensitivity could explain these findings.     

Sinus node function in children with congenital complete atrioventricular block.

AIMS: Children with congenital complete atrioventricular block (CCAVB) often need pacemaker therapy. In these children, it may be preferable to use single-lead VDD pacing, but for VDD pacing a normal sinus node function is required. Our aim was to study sinus node function in children with CCAVB. METHODS AND RESULTS: We longitudinally evaluated sinus rate in 36 children with CCAVB and normal anatomy of the heart. The rate of sinus rhythm on a 12-lead ECG, in Holter recordings, and exercise tests were evaluated at regular intervals. Age at the first visit of the children was 2.5+/-3.3 years (mean+/-SD). Follow-up was 10.6+/-7.3 years. The rate of sinus rhythm on a 12-lead ECG was at every age within the normal values for age (e.g. 0-1 year: 153+/-24 bpm, and 17-18 years: 76+/-4 bpm). Lowest and highest sinus rates in the Holter recordings were normal. During exercise, mean sinus rate in the total group of children increased from 92+/-8 at rest to 171+/-9 bpm at maximal exercise. CONCLUSION: We conclude that sinus node function is normal in children with CCAVB. Because of the normal increase in sinus rate during exercise, a single-lead VDD pacemaker can be safely implanted in these children.     

Functional significance of chronotropic response during chronic amiodarone therapy

Amiodarone, a potent antiarrhythmic agent, has been shown to depress sinus node function. Therefore, this study was undertaken to assess the effect of chronic amiodarone therapy on heart rate during graded exercise testing. 13 patients treated with amiodarone for ventricular arrhythmias were administered symptom-limited graded exercise testing before and 12 weeks after drug therapy. None of the patients had prior evidence of sinus node dysfunction. The mean resting heart rate (beats per minute; bpm) before and after amiodarone therapy was 75 +/- (SD) 13 versus 60 +/- 7 bpm, respectively (p less than 0.005), and the maximal heart rate was 135 +/- 30 versus 109 +/- 24 bpm (p less than 0.005). However, the change in heart rate from rest to maximum exercise (heart rate reserve) was not affected by the drug. Heart rate measured at comparable exercise levels before and during amiodarone therapy was 124 +/- 25 versus 104 +/- 31 (p less than 0.025). There was no change in the systolic blood pressure readings at these respective measured heart rates. Estimated maximal functional capacity before and after drug therapy was 4.9 +/- 1.8 versus 4.7 +/- 2.2 METs (p = NS). In conclusion, chronic amiodarone therapy significantly decreases heart rate at rest and during exercise without altering systolic blood pressure and functional capacity.     

Effect of heart rate on tissue Doppler measures of diastolic function

BACKGROUND: Our aim was to study the independent effect of heart rate (HR) on parameters of diastolic function, particularly mitral annular velocities measured by tissue Doppler imaging (TDI), an effect which is not well understood. METHODS: Sixteen patients with dual chamber pacemakers attending for routine pacemaker review underwent detailed echocardiographic assessment during atrial pacing with intact atrioventricular conduction at baseline and accelerated HRs. Mitral inflow and annular tissue Doppler velocities and systolic strain parameters were compared. RESULTS: Parameters of systolic function were unaffected by increased HR. When these parameters were compared at baseline (mean 67 bpm) and accelerated HR (mean 80 bpm), the following was observed: a significant decrease in early mitral inflow (E) wave (70.5 +/- 5.5 cm/s vs 63.5 +/- 4.9 cm/s, P < 0.02) and early mitral annular (E') velocities (7.0 +/- 0.5 cm/s vs 6.3 +/- 0.6 cm/s, P < 0.003) and a significant increase in mitral inflow A wave (70.3 +/- 4.5 cm/s vs 77.3 +/- 4.4 cm/s, P < 0.05) and late mitral annular (A') velocities (9.3 +/- 0.6 cm/s vs 10.8 +/- 0.5, P < 0.00004). CONCLUSION: Changes in HR have previously unrecognized significant effects on tissue Doppler parameters of diastolic function. Further study is required to determine if tissue Doppler derived annular velocities should be corrected for HR.     

Elevated plasma endothelin-1 levels in coronary sinus during rapid right atrial pacing in patients with slow coronary flow

The aim of the study was to evaluate whether there was an imbalance between endothelin-1 (ET-1) and nitric oxide (NOx) release and diffuse atherosclerotic changes existed in patients with slow coronary flow (SCF). Baseline and post-atrial pacing coronary sinus ET-1 and NOx levels were measured in 19 patients with SCF (11 female, 56 +/- 9 years) and in 14 control subjects (nine female, 54 +/- 7 years). All patients underwent subsequent intravascular ultrasound (IVUS) investigation at the same setting with right atrial pacing. Baseline arterial (12.4 +/- 9.9 vs. 6.3 +/- 5.1 pg/ml, P<0.005) and coronary sinus (12.2 +/- 11.1 vs. 6.4 +/- 6.9 pg/ml, P<0.005) ET-1 plasma levels were higher in patients than in controls. After atrial pacing, concentration of ET-1 level from coronary sinus (24.7 +/- 14.6) significantly increased as compared to baseline (12.4 +/- 9.9, P<0.0001) and control levels (5.3 +/- 6.3, P<0.0001). Additionally, coronary sinus ET-1 level increased significantly with atrial pacing compared to femoral artery ET-1 level (16.3 +/- 8.5, P<0.005) in patients with SCF. After atrial pacing, the femoral artery ET-1 level also increased in patients compared to control level (P<0.0001). No significant differences in arterial and coronary sinus NOx plasma levels were found between the two groups, both at baseline and after pacing. Upon IVUS investigation, the common finding was longitudinally extended massive calcification throughout the epicardial arteries in patients with SCF. Mean intimal thickness was 0.59 +/- 0.18 mm. The data of this study suggest that increased ET-1 levels and insufficient NOx response, as well as the pathological data of IVUS may be associated with coronary microvascular dysfunction and may be the manifestation of early diffuse epicardial atherosclerosis in these patients with SCF.     

Coronary sinus lysophosphatidylcholine accumulation during rapid atrial pacing

The purpose of this study was to determine whether lysophosphatidylcholine (LPC) release from the myocardium could be detected in patients with pacing-induced ischemia. We measured LPC levels in plasma obtained from the coronary sinus in 20 patients undergoing diagnostic atrial pacing stress tests. In 14 patients with pacing-induced ischemia, coronary sinus LPC concentration rose from 69.1 +/- 5.3 microM at baseline to 101.7 +/- 9.0 microM at 4 minutes and to 178.0 +/- 18.0 microM at peak pacing (p less than 0.01). LPC did not increase significantly in 6 nonischemic patients (from 60.8 +/- 7.8 microM at baseline to 70.2 +/- 7.6 microM at peak pacing, difference not significant). LPC did not increase in mixed venous or arterial blood from ischemic patients. Thus, coronary sinus LPC accumulation may be an early marker of ischemia.     

Peripheral arterial disease: an underestimated aetiology of exercise intolerance in chronic obstructive pulmonary disease patients.

OBJECTIVE: To assess the prevalence of peripheral arterial disease and its implications for exercise limitation in chronic obstructive pulmonary disease (COPD) patients. METHOD: One hundred and fifty-one moderate-to-severe COPD patients (forced expiratory volume in 1 s: 37+/-6 SD% predicted) and 73 healthy age-matched control individuals (divided into 31 smokers and 42 nonsmokers) participated in this study. All COPD patients were either exsmokers or current smokers and their tobacco-smoking history was similar to that of healthy smokers. To evaluate the existence of arterial disease, lower limb perfusion pressure impairment was assessed using the ankle brachial index, whereas arterial stiffness was assessed by the pulse wave velocity (PWV). The definition of peripheral arterial disease required an ankle brachial index value of 0.90 or less, whereas the PWV increment was considered to be a direct witness of arterial stiffness increase. A 6-min walk test was performed to assess physical exercise capacity. RESULTS: Prevalence of peripheral arterial disease was higher in COPD patients than in healthy participants (81+/-3 SD; 49+/-5 SD and 9+/-2 SD%, respectively, in COPD, healthy smokers and nonsmokers). PWV mean values were significantly higher in COPD patients compared with healthy smokers and nonsmokers (10.3+/-2.1 SD m/s; 9.2+/-1.3 SD m/s and 8.7+/-2.2 SD m/s, respectively). The distance covered during the 6-min-walk test was associated positively with the degree of peripheral arterial disease (r=0.78; P=0.05) and negatively with the PWV values (r=-0.74; P=0.05). Not only tobacco-smoking history but also COPD severity was shown to influence these associations. CONCLUSION: The effect of peripheral arterial disease on exercise intolerance in COPD seems to be considerable. Therefore, COPD patients participating in a pulmonary rehabilitation programme should profit from a systematic search for arterial disease. Arterial dysfunction has to be taken into account in the multidisciplinary treatment of these patients.     

Effects of atrial pacing on arterial and coronary sinus endothelin-1 levels in syndrome X

Syndrome X may be caused by a coronary microvascular dysfunction, possibly due to abnormalities in coronary endothelial function. Previous studies suggested that endothelin-1 (ET-1) might be involved in the pathogenesis of syndrome X. Baseline arterial and coronary sinus ET-1 levels were measured in 13 patients with syndrome X (10 women, 52+/-7 years) and in 8 control patients (5 women, 46+/-11 years). ET-1 was also measured after atrial pacing in 12 patients with syndrome X and all controls. To simultaneously assess the activity of nitric oxide, guanosine 3'-5'-cyclic monophosphate (cGMP) was also measured in 11 patients with syndrome X and 7 controls. Baseline arterial (2.27+/-0.46 vs. 1.90+/-0.22 pg/ml, p<0.05) and coronary sinus (2.03+/-0.43 vs. 1.68+/-0.28 pg/ml, p = 0.06) ET-1 plasma levels were higher in patients than in controls. After pacing, arterial ET-1 levels did not change in either group and coronary sinus ET-1 levels were also unchanged in controls. In contrast, coronary sinus ET-increased significantly in response to atrial pacing in patients with syndrome X (p = 0.023), and differences between coronary sinus ET-1 levels of patients with syndrome X and controls after pacing became highly significant (2.22+/-0.45 vs. 1.69+/-0.20 pg/ml, respectively, p = 0.006). No significant differences in arterial and coronary sinus cGMP concentrations were found between the 2 groups, both at baseline and after pacing. Our findings suggest that an increased vasoconstrictor activity of microvascular endothelium is present in at least some patients with syndrome X and may be involved in the pathogenesis of the syndrome.     

Withdrawal of hormonal therapy for 4 weeks decreases arterial compliance in postmenopausal women

BACKGROUND: We demonstrated in a previous cross-sectional study that arterial compliance is elevated in postmenopausal women taking estrogen-containing hormonal therapy, which may partially account for the reduction in cardiovascular risk observed. OBJECTIVE: To investigate the effects of withdrawal and recommencement of hormonal therapy, each for 4 weeks, on arterial compliance. METHODS: Seventeen postmenopausal women [aged 56 +/- 4 years (mean +/- SD)] taking long-term hormonal therapy (+HT group) were studied at baseline, 4 weeks after withdrawal of hormonal therapy and again 4 weeks after recommencement. Systemic arterial compliance (SAC), pulse wave velocity (PWV) in the aorto-femoral and femoral-dorsalis pedis regions, and hemodynamic variables were measured at baseline, and at the end of each study intervention. As a time-control, seventeen postmenopausal women (aged 63 +/- 7 years) not taking hormonal therapy (-HT group) were also investigated. RESULTS: SAC significantly decreased from 0.47 +/- 0.06 to 0.40 +/- 0.05 arbitrary compliance units (mean +/- SEM; P < 0.05) after 4 weeks withdrawal from hormonal therapy. PWV in the femoral-dorsalis pedis region was elevated significantly by the withdrawal of hormonal therapy (8.4 +/- 0.4 to 9.4 +/- 0.5 m/s; P < 0.05), but PWV in the aortofemoral region did not change. After therapy had been recommenced for 4 weeks, SAC and PWV in the femoral-dorsalis pedis region were restored to baseline values. The -HT group showed no difference in SAC or PWV, and mean arterial pressure did not change in either group throughout the study period. CONCLUSION: These data suggest that hormonal modulation of distal arterial vascular tone may account for short-term changes in arterial compliance associated with estrogen-containing hormonal therapy.     

Effect of beta-adrenergic stimulation on pulse wave velocity in black and white subjects

BACKGROUND: Reduced beta-adrenergic sensitivity has been reported in black subjects. We hypothesized that beta-adrenergic stimulation by isoproterenol would affect pulse wave velocity (PWV), a marker of arterial stiffness, differently in black and white subjects. METHODS: Healthy normotensive black subjects (n = 21) matched for age, gender, height and body mass index with healthy normotensive white subjects (n = 20), participated in a randomized, double-blind, placebo-controlled cross-over study. The PWV was determined using an automated device at baseline and after 30 min of an equal volume infusion of isoproterenol (8 mug/kg per min) or placebo (dextrose 5%), separated by a washout period of 25 min. RESULTS: At baseline, heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) and PWV were comparable in black and in white subjects. Placebo had no significant effect on haemodynamic variables. Isoproterenol increased HR, SBP and pulse pressure and decreased DBP with a comparable magnitude in both groups. Compared with placebo, isoproterenol decreased carotid-femoral PWV in white (from 5.9 +/- 1.2 to 5.7 +/- 1.1 m/s, means +/- SD, P = 0.05), but not in black subjects (from 6.2 +/- 1.3 to 6.6 +/- 1.7 m/s, P = 0.1). The difference in response between black and white subjects was significant (P = 0.04). Isoproterenol decreased carotid-radial PWV only significantly in white subjects. CONCLUSION: These results are compatible with the hypothesis of an altered beta-adrenergic sensitivity, which is expressed by a blunted effect of isoproterenol on arterial stiffness in black subjects.     

Increased arterial wall stiffness in primary aldosteronism in comparison with essential hypertension

BACKGROUND: Aldosterone has been shown to substantially contribute to the accumulation of collagen fibers and growth factors in the arterial wall, which can increase wall stiffness. This study aimed at comparing arterial stiffness between patients with primary aldosteronism (PA), essential hypertension (EH), and normotensive controls using carotid-femoral pulse wave velocity (PWV) and central augmentation index (AI). METHODS: Thirty-six patients with confirmed PA, 28 patients with EH, and 20 normotensive subjects were investigated by Sphygmocor applanation tonometer. RESULTS: The office blood pressure (BP) at the time of the measurement (PA 167+/-34/92+/-12 mm Hg; EH 166+/-19/91+/-10 mm Hg), age, body mass index (BMI), cholesterol, triglyceride, blood glucose levels were comparable between PA and EH groups. The patients with PA had significantly higher PWV than the EH patients and control subjects (9.8+/-2.6 m/sec v 7.5+/-1.0 m/sec v 5.9+/-0.7 m/sec, respectively; all mutual differences P<.001). The difference in PWV between PA and EH remained statistically significant also after the adjustment for all clinical variables including 24-h BP using multivariate analysis (P=.001). CONCLUSIONS: Arterial wall stiffness is independently increased in PA compared to EH. This could be caused by the deleterious effects of aldosterone excess (potentially modulated by hypernatremia) on the fibrosis and remodeling of the arterial wall.